Abstract
In the present study, we used the potent cocaine analog [3H]WIN 35,428 to map and quantify binding to the dopamine transporter (DAT) within the dorsal striatum, nucleus accumbens, substantia nigra, and ventral tegmental area in young (6-month-old), middle-aged (12-month-old), and aged (18- and 24-month-old) Fischer 344 rats. Quantitative autoradiographic analysis of indirect [3H]WIN 35,428 saturation curves revealed two-site binding for all four brain regions in every age group. The percentage of binding to the high- or low-affinity sites did not differ with age or region and was approximately 50%. However, significant age-related decreases in the overall density (Bmax) of [3H]WIN 35,428-binding sites were observed in the striatum, nucleus accumbens, substantia nigra, and ventral tegmental area. TheBmax within all brain regions declined by more than 15% every 6 months, with the Bmaxin the aged (24-month-old) group being approximately half that measured in the young adult (6-month-old) group. Competition experiments indicated that nomifensine also exhibited two-site binding to the DAT in Fischer 344 rats. No consistent age-related differences in binding affinities were noted with either [3H]WIN 35,428 or nomifensine. Taken together, these results support the hypothesis that functional DATs within the nigrostriatal and mesolimbic systems are down-regulated with age, without changing their affinity for ligands.
Footnotes
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Send reprint requests to: Greg A. Gerhardt, Ph.D., Department of Psychiatry, Box C268-71, University of Colorado Health Sciences Center, 4200 E. Ninth Ave., Denver, CO 80262. E-mail:Greg.Gerhardt{at}uchsc.edu
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↵1 This work was supported by U.S. Public Health Service Grants NS09199, AG06434, and DA04216 and National Institutes of Health Training Grant HD07408. In addition, this work was supported in part by a Level II Research Scientist Development Award (MH01245) from NIMH (G.A.G.) and RSDA Grant DA00174 from NIDA (N.R.Z.).
- Abbreviations:
- DA
- dopamine
- DAT
- dopamine transporter
- F344
- Fischer 344
- Received July 24, 1998.
- Accepted October 1, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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